2,098 research outputs found

    The effects of the English Baccalaureate

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    Fireless cooking

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    Citation: Halm, Helen and McConnel, Fay. Fireless cooking. Senior thesis, Kansas State Agricultural College, 1908.Introduction: The principle of fireless cooking is that of recaloration, or the retention of heat previously generated, through complete insulation. It should, perhaps, be explained here that the word “fireless” is a misnomer. The proper word is “recalorator”, which literally means the conserving of heat, just as a “refrigerator” means the conserving of cold

    Why Don\u27t You Wish To Remember : Why Do You Want To Forget

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    https://digitalcommons.library.umaine.edu/mmb-vp/3765/thumbnail.jp

    Identification of a 17-Nucleotide Splicing Enhancer in HPV-16 L1 that Counteracts the Effect of Multiple hnRNP A1-binding Splicing Silencers

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    Human papillomavirus type 16 (HPV-16) infections can in rare cases persist and cause lesions that may progress to cervical cancer. Cells in the lesions are not permissive for virus production, nor are cervical cancer cells. The intracellular environment is such that it prevents production of the highly immunogenic, viral structural proteins L1 and L2. One may speculate that inhibition of L1 and L2 expression is a prerequisite for persistence and cancer progression.We have therefore investigated how expression of HPV-16 L1 is regulated.We found that the only splice site in the HPV-16 late region, which is used to produce L1 mRNAs, is under control of a splicing enhancer located in the 17 nucleotides immediately downstream of the splice site. However, the function of this enhancer in cervical cancer cells is largely overshadowed by multiple splicing silencers in the late region which bind to hnRNP A1. High levels of hnRNP A1 therefore inhibit HPV-16 L1 expression. Immunohistological analysis of cervical epithelia revealed that hnRNPA1 is expressed primarily in the lower layers of the epithelium. hnRNPA1 is undetectable in terminally differentiated cells that can express HPV-16 late genes, which supports the conclusion that high levels of hnRNP A1 inhibit HPV-16 L1 expression

    A chemical proteomic approach to investigate Rab prenylation in living systems

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    Protein prenylation is an important post-translational modification that occurs in all eukaryotes; defects in the prenylation machinery can lead to toxicity or pathogenesis. Prenylation is the modification of a protein with a farnesyl or geranylgeranyl isoprenoid, and it facilitates protein-membrane and protein-protein interactions. Proteins of the Ras superfamily of small GTPases are almost all prenylated and of these the Rab family of proteins forms the largest group. Rab proteins are geranylgeranylated with up to two geranylgeranyl groups by the enzyme Rab geranylgeranyltransferase (RGGT). Prenylation of Rabs allows them to locate to the correct intracellular membranes and carry out their roles in vesicle trafficking. Traditional methods for probing prenylation involve the use of tritiated geranylgeranyl pyrophosphate which is hazardous, has lengthy detection times, and is insufficiently sensitive. The work described in this thesis developed systems for labelling Rabs and other geranylgeranylated proteins using a technique known as tagging-by-substrate, enabling rapid analysis of defective Rab prenylation in cells and tissues. An azide analogue of the geranylgeranyl pyrophosphate substrate of RGGT (AzGGpp) was applied for in vitro prenylation of Rabs by recombinant enzyme. Alternatively, geranylgeranylated proteins (including Rabs) were labelled with AzGG via metabolic labelling of live cells with AzGGOH. Once Rabs were tagged with an azide moiety they could be labelled via a bioorthogonal ligation reaction with a trifunctional alkyne probe. The probe contained a fluorophore for in-gel fluorescence analysis and a biotin affinity label for affinity purification of labelled proteins. The conditions for protein tagging, labelling, affinity purification and LC-MS/MS analysis were optimised significantly during this work. Affinity purified proteins were identified and in some cases quantified using LC-MS/MS techniques, with iTRAQ labelling for quantification. Rab prenylation was probed in cell culture, in cells treated with the drug Mevastatin and in tissue from mouse models with defects in the prenylation machinery

    Can Seeding in the Clinic Reach a Wide Audience? A Proof of Concept Study on Spreading a Health Message About Juvenile Idiopathic Arthritis Using a Shareable Online Video

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    BACKGROUND: Shareable online video offers the potential for spreading a health message across online and real world social networks. Seeding a message in a clinical setting may be advantageous. OBJECTIVE: To investigate the potential of an online video to spread a health message about juvenile idiopathic arthritis (JIA) when delivered or seeded in a clinical setting and investigate factors that influence sharing behavior. METHODS: Multimethod proof of concept study. Concepts for two different styles of video were developed using focus groups and interviews and reviewed by an online market research panel. We compared dissemination of the two videos from two specialist pediatric rheumatology clinics in NHS Hospitals. Participants were 15 patients, family members, and clinical staff with knowledge of JIA at concept stage; 300 market research panel members in development stage; and 38 patients and their parents or guardians in the seeding stage. Newly diagnosed patients with JIA and/or parents or guardians were invited to view and share an online video with a health message about JIA across real-life and electronic social networks. Main outcome measures were viewing statistics, sharing behavior and patterns, and participant feedback. RESULTS: Of 38 patients and/or their parents or guardians given links, 26 visited the video webpage and shared the link, 2 visited and did not share, and 10 did not visit. Most links were viewed and shared within a few days. A total of 3314 pageviews were recorded with a mean of 89.6 pageviews per link (range 0-1245). Links were accessed from 26 countries, with most viewers in the United Kingdom (82.5%). Mothers were the most active group of sharers. CONCLUSIONS: Distribution of a video link in a clinical setting may be an effective way to spread a health message. Parents or guardians of children with JIA are more likely to share a link than young people. Dissemination depends on a small number of active sharers, the content of the video, and the willingness of participants to share health information about themselves. TRIAL REGISTRATION: UK Clinical Research Network Study Portfolio ID (UKCRN): 13747; http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13747 (Archived by WebCite at http://www.webcitation.org/6eeXlMmM6)

    Interactions between FGF18 and retinoic acid regulate differentiation of chick embryo limb myoblasts

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    During limb development Pax3 positive myoblasts delaminate from the hypaxial dermomyotome of limb level somites and migrate into the limb bud where they form the dorsal and ventral muscle masses. Only then do they begin to differentiate and express markers of myogenic commitment and determination such as Myf5 and MyoD. However the signals regulating this process remain poorly characterised. We show that FGF18, which is expressed in the distal mesenchyme of the limb bud, induces premature expression of both Myf5 and MyoD and that blocking FGF signalling also inhibits endogenous MyoD expression. This expression is mediated by ERK MAP kinase but not PI3K signalling. We also show that retinoic acid (RA) can inhibit the myogenic activity of FGF18 and that blocking RA signalling allows premature induction of MyoD by FGF18 at HH19. We propose a model where interactions between FGF18 in the distal limb and retinoic acid in the proximal limb regulate the timing of myogenic gene expression during limb bud development

    Adenovirus E4orf4 Induces HPV-16 Late L1 mRNA Production

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    The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular splicing factor ASF/SF2 fails to induce L1 mRNA production. Collectively, these results suggest that dephosphorylation of SR proteins by E4orf4 activates HPV-16 late gene expression. Indeed, a mutant ASF/SF2 protein in which the RS-domain had been deleted could itself induce HPV-16 late gene expression, whereas wild type ASF/SF2 could not
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